title: Cyclic N-terminal loop of amylin forms non amyloid fibers.
abstract: We report for the first time, to our knowledge, that the N-terminal loop (N_loop) of amylin (islet amyloid polypeptide (IAPP) residues 1-8) forms extremely long and stable non-β-sheet fibers in solution under the same conditions in which human amylin (hIAPP) forms amyloid fibers. This observation applies to the cyclic, oxidized form of the N_loop but not to the linear, reduced form, which does not form fibers. Our findings indicate a potential role of direct N_loop-N_loop interactions in hIAPP aggregation, which has not been previously explored, with important implications for the mechanism of hIAPP amyloid fiber formation, the inhibitory action of IAPP variants, and the competition between ordered and disordered aggregation in peptides of the calcitonin peptide family.
authors.affiliation: Center for Biological Physics, Arizona State University, Tempe, Arizona; Department of Physics, Arizona State University, Tempe, Arizona.
authors.forename: Stephanie M
authors.initials: SM
authors.lastname: Cope
authors.forename: Sandip
authors.initials: S
authors.lastname: Shinde
authors.forename: Robert B
authors.initials: RB
authors.lastname: Best
authors.forename: Giovanna
authors.initials: G
authors.lastname: Ghirlanda
authors.forename: Sara M
authors.initials: SM
authors.lastname: Vaiana
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D058228:Islet Amyloid Polypeptide / Q000737:chemistry* / Q000378:metabolism; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D058105:Polymerization; D017434:Protein Structure, Tertiary; D051381:Rats
chemical_list: D058228:Islet Amyloid Polypeptide